UNASSIGNED: Male and female Arrb2FLOX mice received intracerebroventricular injection of either adeno-associated virus (AAV)-Cre-GFP (green fluorescent protein) to induce brain-specific deletion of ARRB2 (Arrb2ICV-Cre). Arrb2FLOX mice receiving ICV-AAV-GFP were used as control (Arrb2ICV-Control). Infection with ICV-AAV-Cre primarily targeted the subfornical organ with few off targets. Fluid intake was evaluated using the 2-bottle choice paradigm with 1 bottle containing water and 1 containing 0.15 mol/L NaCl.
UNASSIGNED: Arrb2ICV-Cre mice exhibited a greater pressor response to acute ICV-ANG infusion. At baseline conditions, Arrb2ICV-Cre mice exhibited a significant increase in saline intake compared with controls, resulting in a saline preference. Furthermore, when mice were subjected to water-deprived or sodium-depleted conditions, which would naturally increase endogenous ANG levels, Arrb2ICV-Cre mice exhibited elevated saline intake.
UNASSIGNED: Overall, these data indicate that ARRB2 in selective cardiovascular nuclei in the brain, including the subfornical organ, counterbalances canonical AT1R responses to both exogenous and endogenous ANG. Stimulation of the AT1R/ARRB axis in the brain may represent a novel strategy to treat hypertension.
■雄性和雌性Arrb2FLOX小鼠接受脑室内注射腺相关病毒(AAV)-Cre-GFP(绿色荧光蛋白)以诱导ARRB2的脑特异性缺失(Arrb2ICV-Cre)。将接受ICV-AAV-GFP的Arrb2FLOX小鼠用作对照(Arrb2ICV-对照)。ICV-AAV-Cre的感染主要靶向穹窿下器官,很少脱靶。使用2瓶选择范例评估流体摄入量,其中1瓶含有水,1瓶含有0.15mol/LNaCl。
■Arrb2ICV-Cre小鼠对急性ICV-ANG输注表现出更大的升压反应。在基线条件下,与对照组相比,Arrb2ICV-Cre小鼠的盐水摄入量显着增加,导致盐水偏好。此外,当小鼠受到缺水或贫钠的条件时,这自然会增加内源性ANG水平,Arrb2ICV-Cre小鼠表现出盐水摄入量升高。
■总的来说,这些数据表明,ARRB2在大脑中的选择性心血管核中,包括穹窿下的器官,平衡了典型的AT1R对外源和内源ANG的反应。刺激大脑中的AT1R/ARRB轴可能代表了治疗高血压的新策略。